NIMODIPINE FAILS TO ENHANCE THE ANALGESIC EFFECT OF SLOW-RELEASE MORPHINE IN THE EARLY PHASES OF CANCER PAIN TREATMENT

We assessed nimodipine's ability to increase the analgesic effect of m orphine in 32 patients suffering from cancer pain in a double-blind, p lacebo controlled cross-over study. Morphine administration began a fe w days before the start of the study. The analgesic effects of two com binations were compared: morphine (M) plus placebo (P) and morphine pl us 90 mg/24 h of nimodipine (N). The study lasted 8 days, including th e wash-out period, and the following sequence of treatments was applie d: M + P or M + N on days 1, 2 and 3; only M on days 4 and 5; and M N or M + P on days 6, 7 and 8. Morphine dose was individualised accord ing to the intensity of the patient's pain and the same dose was maint ained throughout the study period. Analgesic response was evaluated us ing four 10 cm visual analogue scales of quantitative variables for pa in intensity, pain relief, sleep quality and mood. A verbal rating of qualitative variables was also scored following validated descriptors of pain in the Spanish language. No significant statistical difference s were found in analgesic effect between combined treatment with nimod ipine or placebo, as measured on any of the scales. In order to take i nto account both the short duration of treatment (8 days), and nimodip ine's pharmacokinetic characteristics (half-life of 6 h and steady sta te of 36 h), we compared treatment with nimodipine or placebo on the t hird day of use, at which time, likewise, there were no statistically significant differences on any of the scales. However, when the same s tatistical tests were used for comparison of results with pre-treatmen t baseline values, highly significant differences between mean scores on the scales for pain relief and pain intensity were found. Based on these negative results we conclude that nimodipine given orally at a d ose of 30 mg every 8 h does not enhance analgesia when associated with morphine in the early phases of treatment for cancer pain. Our study also gives clear evidence of a placebo effect.